The specific aim of this application is to test the feasibility of developing a long-lasting, implantable probe for rapid measurement of multiple neurochemicals in the brain. Currently, neuroscience research is limited to three techniques for measuring the concentrations of neurochemicals in vivo; microdialysis to obtain average concentrations over a relatively long time period (5-20 minutes), enzyme-based biosensors to detect a single neurochemical every second over a relatively large spatial area (500m length electrode), and carbon-fiber microelectrodes to detect dopamine with fast scan cyclic voltammetry (FSCV). A new tool is required for rapid detection of concentrations of multiple neurochemicals with spatial resolution on the cellular level. Such a tool would allow neuroscience researchers to ask new questions about the mechanisms behind disease states and behaviors, such as alcohol drinking. The proposed neural probe fulfills this need by detecting two neurochemicals every 4 seconds with 50 m spatial resolution. SB Microsystems has already developed a proprietary MEMS process for fabricating implantable, multi-site neural probes for studying the rat brain. Our existing probes have the feature size necessary for a 10-fold spatial resolution improvement over the available enzyme-based electrodes. The proposed probe will build on our existing platform by functionalizing the probe site surfaces with molecules for the detection of specific neurochemicals. Detection of multiple neurochemicals will be achieved by patterning different neurochemical- specific detection molecules onto adjacent probe sites. Our Phase I application will determine feasibility for commercialization of these probes by; 1) improving functionalized probe fabrication by adjusting aptamer molecule modifications, immobilization technique, and electrical signal detection to achieve the best possible sensitivity and time response, 2) developing a potentiostat circuit based for detection, 3) developing two aptamer molecules; one that is specific, sensitive, and long-lasting for ethanol, and another for GABA. Next, we will 4) functionalize the probe to detect multiple analytes with the newly develop aptamers and 5) implant probes into mice for in vivo data collection. Success in this Phase I feasibility study will be determined by the accurate detection of physiologically relevant concentrations of ethanol and GABA by probes that are stable in vivo for 2 days. In Phase II, we plan to develop more aptamers that can be applied to our probes for the detection of more than 2 neurotransmitters. We will use principles of robust design to turn our prototype into a commercial product. The attached letters of support indicate that we may be able to sell a successful prototype from Phase I to neuroscience researchers. !